1. ^*Department of Neurosurgery, Baylor College of Medicine, Houston, Texas 77030
2. ^†Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030
3. ^**Department of Neurology, Baylor College of Medicine, Houston, Texas 77030
4. ^§Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030
5. Department of Microbiology and Immunology, Baylor College of Medicine, Houston, Texas 77030
6. ^††Department of Pathology, Baylor College of Medicine, Houston, Texas 77030
7. ^¶Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030
8. ^‡Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas 77030
9. ^‡‡Institute for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, New York, New York, 10029

Correspondence: Todd W. Trask, Department of Neurosurgery, Baylor College of Medicine, 6560 Fannin, Suite 944, Houston, TX 77030. Fax: 713.798.3739. E-mail: ttrask@bcm.tmc.edu.

Received 29 November 1999; Accepted 25 January 2000.

Abstract

Between December 1996 and September 1998, 13 patients with advanced recurrent malignant brain tumors (9 with glioblastoma multiforme, 1 with gliosarcoma, and 3 with anaplastic astrocytoma) were treated with a single intratumoral injection of 2 10⁹, 2 10¹⁰, 2 10¹¹, or 2 10¹² vector particles (VP) of a replication-defective adenoviral vector bearing the herpes simplex virus thymidine kinase gene driven by the Rous sarcoma virus promoter (Adv.RSVtk), followed by ganciclovir (GCV) treatment. The VP to infectious unit ratio was 20:1. Our primary objective was to determine the safety of this treatment. Injection of Adv.RSVtk in doses 2 10¹¹ VP, followed by GCV, was safely tolerated. Patients treated with the highest dose, 2 10¹² VP, exhibited central nervous system toxicity with confusion, hyponatremia, and seizures. One patient is living and stable 29.2 months after treatment. Two patients survived >25 months before succumbing to tumor progression. Ten patients died within 10 months of treatment, 9 from tumor progression and 1 with sepsis and endocarditis. Neuropathologic examination of postmortem tissue demonstrated cavitation at the injection site, intratumoral foci of coagulative necrosis, and variable infiltration of the residual tumor with macrophages and lymphocytes.